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Construction of functional cultured neural circuitry

Research Project

Project/Area Number 20K20643
Research Category

Grant-in-Aid for Challenging Research (Pioneering)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 90:Biomedical engineering and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

IKEUCHi Yoshiho  東京大学, 生産技術研究所, 准教授 (30740097)

Co-Investigator(Kenkyū-buntansha) ティクシェ三田 アニエス  東京大学, 生産技術研究所, 准教授 (00334368)
Project Period (FY) 2020-07-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000)
Fiscal Year 2023: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2021: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2020: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywords神経 / オルガノイド / 組織工学 / 可塑性 / in vitro / 神経回路組織 / 学習 / 神経細胞 / iPS細胞 / 脳
Outline of Research at the Start

本研究では脳内の神経回路を単純化して体外で再現するために、ヒトiPS細胞を用いて作製した二つの人工脳組織(オルガノイド)の間をたくさんの双方に向けて伸びた軸索を介して接続します。この回路のような神経組織が学習できるように神経回路組織を最適化したり、神経活動に応じて最適な刺激を与えるようなシステムを構築したりして、神経回路組織の活動を制御します。最終的には、神経回路が機能する仕組みを理解する事を目指しています。

Outline of Final Research Achievements

This research aimed to simplify the complexity of neural circuits in the brain and recreate them outside the body to understand their functions and mechanisms. Specifically, it sought to create functional "cultured human brain circuit tissues" by connecting multiple brain region-mimicking organoids. Organoids mimicking the cerebrum, midbrain, thalamus, basal ganglia, and spinal cord were produced and connected to form circuit tissues. Transmission rules of action potentials and changes in response to stimulation were observed, and culturing methods were established along with the development of unique techniques. In pattern recognition tasks, slight improvements in performance were noted, yielding significant insights for future research. Moving forward, the aim is to achieve a more advanced recreation of neural circuits and learning functions, with applications for developing models and treatments for neurological diseases.

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義は、ヒトの脳内神経回路を体外で再現し、その機能と学習メカニズムを理解する新たな方法を確立した点にある。神経回路の複雑な動態を解明するための基礎的手法を開拓し、新たな研究分野を切り開くものである。また、神経オルガノイドに計算処理をさせることが世界的に期待され始めているため、先行して知見を得られたことは意義深い。得られた知見を基に神経疾患のモデル構築や新たな治療法の開発が期待される。特に、脳の可塑性や学習機能の理解が進むことで、認知症や精神疾患などの治療に革新をもたらす可能性がある。さらに、人工知能やロボティクス分野への応用も見込まれ、幅広い社会的貢献が期待される。

Report

(3 results)
  • 2023 Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (20 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (2 results) Journal Article (12 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 12 results,  Open Access: 4 results) Presentation (6 results) (of which Int'l Joint Research: 1 results)

  • [Int'l Joint Research] ボルドー大学/LAAS(フランス)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] IMBA(オーストリア)

    • Related Report
      2022 Research-status Report
  • [Journal Article] High-throughput Assessment of Mitochondrial Protein Synthesis in Mammalian Cells Using Mito-FUNCAT FACS2023

    • Author(s)
      Saito Hironori、Osaki Tatsuya、Ikeuchi Yoshiho、Iwasaki Shintaro
    • Journal Title

      BIO-PROTOCOL

      Volume: 13 Issue: 3

    • DOI

      10.21769/bioprotoc.4602

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human sensory neurons modulate melanocytes through secretion of RGMB2022

    • Author(s)
      Chow Siu Yu A.、Nakayama Kazuki、Osaki Tatsuya、Sugiyama Maki、Yamada Maiko、Takeuchi Hirotaka、Ikeuchi Yoshiho
    • Journal Title

      Cell Reports

      Volume: 40 Issue: 12 Pages: 111366-111366

    • DOI

      10.1016/j.celrep.2022.111366

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Two-photon, red light uncaging of alkyl radicals from organorhodium(III) phthalocyanine complexes2022

    • Author(s)
      Murata Kei、Saibe Yuki、Uchida Mayu、Aono Mizuki、Misawa Ryuji、Ikeuchi Yoshiho、Ishii Kazuyuki
    • Journal Title

      Chemical Communications

      Volume: 58 Issue: 80 Pages: 11280-11283

    • DOI

      10.1039/d2cc03672j

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Advances in construction and modeling of functional neural circuits in vitro2022

    • Author(s)
      Chow Siu Yu A.、Hu Huaruo、Osaki Tatsuya、Levi Timoth?e、Ikeuchi Yoshiho
    • Journal Title

      Neurochemical Research

      Volume: 47 Issue: 9 Pages: 2529-2544

    • DOI

      10.1007/s11064-022-03682-1

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Modeling Axonal Degeneration Using Motor Nerve Organoids2022

    • Author(s)
      Chow Siu Yu A.、Nakanishi Yui、Kaneda Shohei、Ikeuchi Yoshiho
    • Journal Title

      Methods Mol Biol.

      Volume: 2515 Pages: 89-97

    • DOI

      10.1007/978-1-0716-2409-8_6

    • ISBN
      9781071624081, 9781071624098
    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Localised light delivery on melanoma cells using optical microneedles2022

    • Author(s)
      Wu Xiaobin、Park Jongho、Chow Siu Yu A.、Kasuya Maria Carmelita Z.、Ikeuchi Yoshiho、Kim Beomjoon
    • Journal Title

      Biomedical Optics Express

      Volume: 13 Issue: 2 Pages: 1045-1045

    • DOI

      10.1364/boe.450456

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Self-Deformable Flexible MEMS Tweezer Composed of Poly(Vinylidene Fluoride)/Ionic Liquid Gel for Electrical Measurements and Soft Gripping2022

    • Author(s)
      Yamaguchi Takafumi、Usami Naoto、Misumi Kei、Toyokura Atsushi、Higo Akio、Ono Shimpei、Hwang Gilgueng、Larrieu Guilhem、Ikeuchi Yoshiho、Tixier-Mita Agnes、Saito Ken、Levi Timothee、Mita Yoshio
    • Journal Title

      Journal of Microelectromechanical Systems

      Volume: 31 Issue: 5 Pages: 802-812

    • DOI

      10.1109/jmems.2022.3187428

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Three-dimensional imaging of the hyperpigmented skin of senile lentigo reveals underlying higher density intracutaneous nerve fibers2021

    • Author(s)
      Nakayama Kazuki、Sassa Shoko、Sugiyama Maki、Kurosumi Motonori、Nishikori Shu、Chow Siu Yu A.、Suzuki Tamio、Ikeuchi Yoshiho
    • Journal Title

      Journal of Dermatological Science

      Volume: - Issue: 1 Pages: 72-75

    • DOI

      10.1016/j.jdermsci.2021.01.010

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Loss of Ftsj1 perturbs codon-specific translation efficiency in the brain and is associated with X-linked intellectual disability2021

    • Author(s)
      Nagayoshi Y.、Chujo T.、Hirata S.、Nakatsuka H.、Chen C.-W.、Takakura M.、Miyauchi K.、Ikeuchi Y.、Carlyle B. C.、Kitchen R. R.、Suzuki T.、Katsuoka F.、Yamamoto M.、Goto Y.、Tanaka M.、Natsume K.、Nairn A. C.、Suzuki T.、Tomizawa K.、Wei F.-Y.
    • Journal Title

      Science Advances

      Volume: 7 Issue: 13

    • DOI

      10.1126/sciadv.abf3072

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Light-inducible control of cellular proliferation and differentiation by a Hedgehog signaling inhibitor2021

    • Author(s)
      Misawa Ryuji、Minami Tsuyoshi、Okamoto Akimitsu、Ikeuchi Yoshiho
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 38 Pages: 116144-116144

    • DOI

      10.1016/j.bmc.2021.116144

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Three-Dimensional Motor Nerve Organoid Generation2020

    • Author(s)
      Osaki Tatsuya、Chow Siu Yu A.、Nakanishi Yui、Hernandez Joel、Kawada Jiro、Fujii Teruo、Ikeuchi Yoshiho
    • Journal Title

      Journal of Visualized Experiments

      Volume: 163 Issue: 163

    • DOI

      10.3791/61544

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] TFT sensor array for real-time cellular characterization, stimulation, impedance measurement and optical imaging of in-vitro neural cells2020

    • Author(s)
      Shaik Faruk Azam、Ihida Satoshi、Ikeuchi Yoshiho、Tixier-Mita Agnes、Toshiyoshi Hiroshi
    • Journal Title

      Biosensors and Bioelectronics

      Volume: 169 Pages: 112546-112546

    • DOI

      10.1016/j.bios.2020.112546

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] From real-time single to multicompartmental Hodgkin-Huxley neurons on FPGA for bio-hybrid systems.2022

    • Author(s)
      Beaubois R, Khoyratee F, Branchereau P, Ikeuchi Y, Levi T
    • Organizer
      Annu Int Conf IEEE Eng Med Biol Soc.
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Advanced Complexity and Plasticity of Neural Activity in Reciprocally Connected Human Cerebral Organoids2022

    • Author(s)
      Yoshiho Ikeuchi
    • Organizer
      第45回日本神経科学大会/第65回日本神経化学会大会/第32回日本神経回路学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Organoids-on-a-chip models for understanding neuronal circuits and underlying protein synthesis regulations2022

    • Author(s)
      Yoshiho Ikeuchi
    • Organizer
      The 28th Tokyo RNA Club
    • Related Report
      2022 Research-status Report
  • [Presentation] 末梢神経オルガノイドチップの開発と応用2022

    • Author(s)
      池内与志穂
    • Organizer
      日本末梢神経学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 大脳オルガノイドをつなげて神経回路を創る2022

    • Author(s)
      池内与志穂
    • Organizer
      細胞を創る研究会
    • Related Report
      2022 Research-status Report
  • [Presentation] 神経オルガノイドを用いた神経のしなやかな翻訳調節とその機能の探索2022

    • Author(s)
      池内与志穂
    • Organizer
      第95回日本生化学会
    • Related Report
      2022 Research-status Report

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Published: 2020-08-03   Modified: 2025-01-30  

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